Ortho-hydroxybenzyl-aroyl-amine arsonic acids and process of making same



Patented Dec. 8, 1931 UNITED STATES PATENT OFFICE WERNER SCHMIDT, OFFRANKFORT-ON-THE-MAIN/MAINKUR, GERMANY, ASSIGNOR TO WINTHROP CHEMICALCOMPANY, INC., OF NEW YOR-K, N. Y., A CORPORATION OF NEW YORKORTI-IOI-IYDEROXYBENZYL-AROYL-AMINE ARSONIG ACIDS AND PROCESS OF MAKINGSAME No Drawing. Application filed May 22, 1928, Serial No. 279,855, andin Germany May 31, 1927.

The present invention relates to new orthohydroxy benzyl aroylaminearsonic. acids and to a process of preparing the same.

I have found that ortho-hydroxy-benzylaroylamine-arsonic acids of thegeneral formula:

Y o Ha-lTT-OO X x AsOaHz wherein the Xs stand for hydrogen atoms whichmay be jointly replaced by a CO-group and Y stands for hydrogen, methylor chlorine, are obtained by condensing para-hydroxy-phenyl-arsonicacids of the general formula:

an acid solution with hydroxy-methyl-aroylamine compounds of the generalformula:

wherein X has the aforesaid signification.

The new compounds obtained by my process are identical with the productsmentioned in my copending application Serial No. 27 9,854, filed May 22,1928. By saponification they are transformed into the correspondinghydroxybenzylamine arsonic acids, which are the subject matter ofmycopending application, Serial No. 279,854. They possess a goodtherapeutical activity and are of an especial importance because theylack any neurotoxic action. They may also be used as starting materialsfor manufacturing other pharmaceutical products.

In order to further illustrate my invention the following examplesaregiven, 'the parts being by weight and all temperatures in Centigradedegrees; but I wish to be understood that my invention is not limited tothe examples given nor to the exact conditions mentioned therein.

Ewample 1 r 22 parts of the sodium salt of the p-h droxy-phenyl-arsonicacid are mixed with 15 parts of hydroxymethyl-benzoyl-amine and themixture is introduced into 600 parts of sulfuric acid of 66 B. at 5-15",while stirring and cooling With water. The solution thus obtained isallowed to stand for 12 hours, then it is poured on ice-water, partiallyneutralized by means of soda and precipitated with common salt. The4-hydroxy-5- benzyl-benzoylamine-l-arsonic acid of the formula:

AsOaHz Example .2

300 parts of the sodium salt of the d-hydroxy-phenyl-arsonic acid and180 parts of hydroxymethyl-phthalic imide are Well mixed and introducedwhile cooling into 600 parts of sulfuric acid of 66 B., the temperaturebeing maintained below 30. After about 12 hours the condensation productis separated by pouring the reaction mass on ice-water. The precipitateis filtered 011:,

washed with water and purified by dissolving it in an acetate solutionand precipitating again with water. The new l-hydroxy- 5-benzyl-phthalicimide-l-arsonic acid corresponds to the formula:

AsOsH:

It crystallizes from a lar e quantity of hot water in the form ofcolorless needles melting at about 276. It is soluble in hot water, indilute alkalies and in warm acetate solutions, diflicultly soluble incold water and in dilute spirit, insoluble in mineral acids, in ether,benzene and benzine. It is identical with the product describedsub-paragraph (b) in Example 2 of my copending application Serial No.279,854. As there explained it may be saponified to the4;-hydroXy-5-benzylatnine-Larsonic acid.

Example 3 320 parts of the sodium salt of the3-chlorol-hydroxy-phenyl-arsonic acid and 180 parts ofhydroxymethyl-phthalic imide are well mixed and introduced, whilecooling and stirring, into 600 parts of sulfuric acid of 66 B. at atemperature of -25". After 24: hours the mass is poured on ice-water.The white crystalline precipitate thus formed is filtered off, washedwith water until it shows a neutral reaction and dissolved in thecalculated amount of acold soda solution. The solution is filtered andthe new compound is precipitated by acidifying the solution.

The 3-chlor0- l-hydroXy-5-benzyl-phthalic imide-l-arsonic acidcorresponds to the formula:

AsOaH:

Example 4 i If in the Example 3 the 8-chl0ro-l-hydroXy-phenyl arsonicacid is replaced by the corresponding amount of the3-methyll-hydroxyphenyl arsonic acid and otherwise the process iscarried out in the same manner, the new 3 methyl 4 hydroxy 5benzylphthalic imide-l-arsonic acid corresponding to the formula C 0--6113 CH2N l ASOaHI AS 03H:

wherein Y stands for hydrogen, methyl or chlorine, in an acid solutionwith hydroxymethyLarOyl-amine compounds of the general formula:

wherein the Xs stand for hydrogen atoms which may be jointly replaced bya CO- group.

2. As new products ortho-hydroxy-benzyl-aroylamine arsenic acids of thegeneral formula:

wherein the Xs stand for hydrogen atoms whichmay be jointly replaced bya CO- group and Y stands for hydrogen, methyl or chlorine, whichproducts are white crystalline substances, having a definite meltingpoint, easily soluble in alkalies, difficultly soluble in water, spiritand acetone, insoluble in ether, benzene and in mineral acids.

3. As a neW product the 4-hydroXy-5-benzyl phthalic imide 1-arsonic acidof the formula:

I ASOaHz whlch product represents when crystallized from hot watercolorless needles melting at about 276, soluble in hot water, in dilutealkalies and in a Warm alkali acetate solution, diificultly soluble incold water and in dilute spirit, insoluble in mineral acids, in ether,benzene and benzine.

In testimony whereof, I affix my signature.

WERNER SCHMIDT.

